Accepted: 7 September 2017 DOI: 10.1111/petr.13068
ORIGINAL ARTICLE
Proteinuria in pediatric renal transplant recipients Songül Yılmaz1
| Z. Birsin Özçakar1 | Aysel Taktak2 | Eda Didem Kurt-Şükür1 |
Nilgün Çakar1 | Fatoş Yalçınkaya1 1 Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey 2
Department of Pediatric Nephrology, Ankara Child Health Hematology and Oncology Education Research Hospital, Ankara, Turkey Correspondence Fatoş Yalçınkaya, Ankara Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları AD, Pediatrik Nefroloji, Ankara, Turkey. Email: [email protected]
Abstract Proteinuria has been shown to be an important and potentially treatable risk factor for graft loss. The aim of this study was to evaluate prevalence, etiology, and outcome of proteinuria during the follow-up of children with renal transplantation. We retrospectively reviewed the files of renal transplanted children between 2006 and 2016 in our center. All patients were interpreted with respect to the demographic data and clinical and laboratory features including information about proteinuria. Chi-square test and Mann-Whitney U test were used for analysis. Fifty-two children were eligible for the study. Proteinuria was observed in 34 (65%) and nephrotic range proteinuria was detected in 5 (9.6%) patients. Etiology of proteinuria could be identified in 21 patients. Acute rejection and uncontrolled hypertension were the most frequent causes of proteinuria. Proteinuria had resolved during the follow-up in 59% of the patients. We found that children with and without proteinuria had similar glomerular filtration rate at the end of 50 months of follow-up period. Proteinuria seems to be a common complication in renal transplant recipients. Graft functions can be preserved by immediate evaluation of increasing proteinuria, and by fixing treatable causes rapidly and efficiently during the follow-up in majority of the patients. KEYWORDS
children, proteinuria, transplantation
1 | INTRODUCTION
renal transplantation was evaluated in only a few studies and these
Proteinuria is a common complication after renal transplantation, and
were generally cross-sectional studies investigating the prevalence
its prevalence was reported to vary considerably, from 11% to 82%
and risk factors for proteinuria.2,5-7 The aim of this study was to eval-
in adult and pediatric populations.1,2 In recent years, there has been
uate the prevalence, etiology, and outcome of proteinuria during the
a growing interest about the impact of proteinuria in these patients
follow-up of children with renal transplantation.
and multiple risk factors for proteinuria were reported including acute or chronic rejection, obesity, hypertension, and recurrent or de novo glomerulonephritis.3
2 | MATERIAL AND METHODS
Increased urinary protein excretion has been shown to be an important and potentially treatable risk factor for graft loss like native
We retrospectively reviewed the files of renal transplanted children in
kidneys in adults.4 However, despite these negative effects on allograft
our center. Patients with a follow-up period of at least 6 months after
survival, management and evidence-based therapies for the treatment
transplantation were included in the study. Evaluation of proteinuria
of proteinuria are lacking. In the pediatric population, proteinuria after
was carried out 1 month after transplantation. Proteinuria within the first month of transplantation was not taken into consideration in
Abbreviations: ABPM, ambulatory BP monitoring; ACEI, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; BKV, BK virus; BMI, body mass index; BP, blood pressure; FSGS, focal segmental glomerulosclerosis; GFR, glomerular filtration rate.
Pediatric Transplantation. 2017;e13068. https://doi.org/10.1111/petr.13068
order to exclude the contribution of early post-transplant period and native kidneys for proteinuria development.
wileyonlinelibrary.com/journal/petr
© 2017 John Wiley & Sons A/S. | 1 of 5 Published by John Wiley & Sons Ltd
|
YILMAZ et al.
2 of 5
For each patient, data were recorded as outlined below:
T A B L E 1 Etiology of end-stage renal disease n = 52 (%)
• Clinical information, including age at transplantation, gender, underlying disease, donor type (deceased or living donor), immuno-
Congenital anomalies of the kidney and urinary tract
suppressive medication, BMI at the time of proteinuria and at last
Nephrotic syndrome
7 (13.4)
FSGS
4 (7.7)
Cystic kidney disease
3 (5.7)
Amyloidosis (due to familial Mediterranean fever)
4 (7.7)
visit, BP and the use of antihypertensive therapy. • Laboratory findings, including urinalysis, 24-hour urinary protein excretion, serum protein and albumin level, GFR at the time of proteinuria and at last visit, renal biopsy findings, therapy for protein-
Tubulointerstitial disease
uria, and identified causes.
Cystinosis
We checked proteinuria with a urine dipstick method during every outpatient visit. Spot urine protein/creatinine ratio and 24-hour urine analysis were ordered when proteinuria was detected with the dipstick method. Proteinuria was assessed by collecting 24-hour urine at least once within the first month after transplantation, at least every
21 (40.8)
11 (21) 2 (3.8)
Hemolytic uremic syndrome
1 (1.9)
Unknowna
3 (5.7)
a
One of the unknown patients was diagnosed as primary hyperoxaluria after transplantation.
3 months between months 1 and 12, and at least annually ≥1 year post-transplant, even if urine tests were normal. Proteinuria was mea-
be identified in 21 patients and is given in Table 2. The amount of pro-
sured daily in the first 2-3 weeks post-transplantation in patients with
teinuria ranged from 5 to 179 mg/m2/h with a median of 10.6 mg/
idiopathic FSGS.
m2/h and continued 13 months (range 1-72 months). Nephrotic range
Pathological and nephrotic proteinuria was defined as urinary pro-
proteinuria was detected in 5 (9.6%) patients: two with recurrent
tein excretion >4 and >40 mg/m2/h, respectively, in a 24-hour urinal-
FSGS, one with de novo amyloidosis, one with acute rejection, and
ysis. Allograft biopsies were performed after clinical and laboratory
one with uncontrolled hypertension. Renal biopsy was performed in
evaluation.
16 patients and showed acute cellular rejection in 5, humoral rejection
Hypertension was defined as blood pressure values ≥95th percentile according to gender, age, and height. Twenty-four-hour ABPM
in 2, FSGS recurrence in 2, and de novo amyloidosis and hyperoxaluria each in 1 patient, and 5 patients had normal biopsy.
was performed if casual BP measurements were found to be elevated.
During the follow-up, proteinuria disappeared in 5 patients with
If casual measurements were normal and patient was on antihyper-
acute rejection and decreased in amount in the remaining two. Six
tensive treatment, it was classified as controlled hypertension, but
patients had uncontrolled hypertension and proteinuria. With strict
if blood pressure measurements were high, despite antihypertensive
blood pressure control (under 75th percentiles according to age, gen-
treatment, it was classified as uncontrolled hypertension.
der, and height), proteinuria resolved in 3 of them. Despite specific
The Research Ethics Committee of Ankara University School of
therapy, including plasmapheresis and rituximab, two patients with
Medicine approved the study. SPSS for Windows 22.0 was used for
FSGS recurrence continued to have nephrotic range proteinuria and
statistical analysis. The chi-square test and Mann-Whitney U test were
graft loss was observed in both cases. These patients did not receive
used for analysis. A P value
ORIGINAL ARTICLE
Proteinuria in pediatric renal transplant recipients Songül Yılmaz1
| Z. Birsin Özçakar1 | Aysel Taktak2 | Eda Didem Kurt-Şükür1 |
Nilgün Çakar1 | Fatoş Yalçınkaya1 1 Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey 2
Department of Pediatric Nephrology, Ankara Child Health Hematology and Oncology Education Research Hospital, Ankara, Turkey Correspondence Fatoş Yalçınkaya, Ankara Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları AD, Pediatrik Nefroloji, Ankara, Turkey. Email: [email protected]
Abstract Proteinuria has been shown to be an important and potentially treatable risk factor for graft loss. The aim of this study was to evaluate prevalence, etiology, and outcome of proteinuria during the follow-up of children with renal transplantation. We retrospectively reviewed the files of renal transplanted children between 2006 and 2016 in our center. All patients were interpreted with respect to the demographic data and clinical and laboratory features including information about proteinuria. Chi-square test and Mann-Whitney U test were used for analysis. Fifty-two children were eligible for the study. Proteinuria was observed in 34 (65%) and nephrotic range proteinuria was detected in 5 (9.6%) patients. Etiology of proteinuria could be identified in 21 patients. Acute rejection and uncontrolled hypertension were the most frequent causes of proteinuria. Proteinuria had resolved during the follow-up in 59% of the patients. We found that children with and without proteinuria had similar glomerular filtration rate at the end of 50 months of follow-up period. Proteinuria seems to be a common complication in renal transplant recipients. Graft functions can be preserved by immediate evaluation of increasing proteinuria, and by fixing treatable causes rapidly and efficiently during the follow-up in majority of the patients. KEYWORDS
children, proteinuria, transplantation
1 | INTRODUCTION
renal transplantation was evaluated in only a few studies and these
Proteinuria is a common complication after renal transplantation, and
were generally cross-sectional studies investigating the prevalence
its prevalence was reported to vary considerably, from 11% to 82%
and risk factors for proteinuria.2,5-7 The aim of this study was to eval-
in adult and pediatric populations.1,2 In recent years, there has been
uate the prevalence, etiology, and outcome of proteinuria during the
a growing interest about the impact of proteinuria in these patients
follow-up of children with renal transplantation.
and multiple risk factors for proteinuria were reported including acute or chronic rejection, obesity, hypertension, and recurrent or de novo glomerulonephritis.3
2 | MATERIAL AND METHODS
Increased urinary protein excretion has been shown to be an important and potentially treatable risk factor for graft loss like native
We retrospectively reviewed the files of renal transplanted children in
kidneys in adults.4 However, despite these negative effects on allograft
our center. Patients with a follow-up period of at least 6 months after
survival, management and evidence-based therapies for the treatment
transplantation were included in the study. Evaluation of proteinuria
of proteinuria are lacking. In the pediatric population, proteinuria after
was carried out 1 month after transplantation. Proteinuria within the first month of transplantation was not taken into consideration in
Abbreviations: ABPM, ambulatory BP monitoring; ACEI, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; BKV, BK virus; BMI, body mass index; BP, blood pressure; FSGS, focal segmental glomerulosclerosis; GFR, glomerular filtration rate.
Pediatric Transplantation. 2017;e13068. https://doi.org/10.1111/petr.13068
order to exclude the contribution of early post-transplant period and native kidneys for proteinuria development.
wileyonlinelibrary.com/journal/petr
© 2017 John Wiley & Sons A/S. | 1 of 5 Published by John Wiley & Sons Ltd
|
YILMAZ et al.
2 of 5
For each patient, data were recorded as outlined below:
T A B L E 1 Etiology of end-stage renal disease n = 52 (%)
• Clinical information, including age at transplantation, gender, underlying disease, donor type (deceased or living donor), immuno-
Congenital anomalies of the kidney and urinary tract
suppressive medication, BMI at the time of proteinuria and at last
Nephrotic syndrome
7 (13.4)
FSGS
4 (7.7)
Cystic kidney disease
3 (5.7)
Amyloidosis (due to familial Mediterranean fever)
4 (7.7)
visit, BP and the use of antihypertensive therapy. • Laboratory findings, including urinalysis, 24-hour urinary protein excretion, serum protein and albumin level, GFR at the time of proteinuria and at last visit, renal biopsy findings, therapy for protein-
Tubulointerstitial disease
uria, and identified causes.
Cystinosis
We checked proteinuria with a urine dipstick method during every outpatient visit. Spot urine protein/creatinine ratio and 24-hour urine analysis were ordered when proteinuria was detected with the dipstick method. Proteinuria was assessed by collecting 24-hour urine at least once within the first month after transplantation, at least every
21 (40.8)
11 (21) 2 (3.8)
Hemolytic uremic syndrome
1 (1.9)
Unknowna
3 (5.7)
a
One of the unknown patients was diagnosed as primary hyperoxaluria after transplantation.
3 months between months 1 and 12, and at least annually ≥1 year post-transplant, even if urine tests were normal. Proteinuria was mea-
be identified in 21 patients and is given in Table 2. The amount of pro-
sured daily in the first 2-3 weeks post-transplantation in patients with
teinuria ranged from 5 to 179 mg/m2/h with a median of 10.6 mg/
idiopathic FSGS.
m2/h and continued 13 months (range 1-72 months). Nephrotic range
Pathological and nephrotic proteinuria was defined as urinary pro-
proteinuria was detected in 5 (9.6%) patients: two with recurrent
tein excretion >4 and >40 mg/m2/h, respectively, in a 24-hour urinal-
FSGS, one with de novo amyloidosis, one with acute rejection, and
ysis. Allograft biopsies were performed after clinical and laboratory
one with uncontrolled hypertension. Renal biopsy was performed in
evaluation.
16 patients and showed acute cellular rejection in 5, humoral rejection
Hypertension was defined as blood pressure values ≥95th percentile according to gender, age, and height. Twenty-four-hour ABPM
in 2, FSGS recurrence in 2, and de novo amyloidosis and hyperoxaluria each in 1 patient, and 5 patients had normal biopsy.
was performed if casual BP measurements were found to be elevated.
During the follow-up, proteinuria disappeared in 5 patients with
If casual measurements were normal and patient was on antihyper-
acute rejection and decreased in amount in the remaining two. Six
tensive treatment, it was classified as controlled hypertension, but
patients had uncontrolled hypertension and proteinuria. With strict
if blood pressure measurements were high, despite antihypertensive
blood pressure control (under 75th percentiles according to age, gen-
treatment, it was classified as uncontrolled hypertension.
der, and height), proteinuria resolved in 3 of them. Despite specific
The Research Ethics Committee of Ankara University School of
therapy, including plasmapheresis and rituximab, two patients with
Medicine approved the study. SPSS for Windows 22.0 was used for
FSGS recurrence continued to have nephrotic range proteinuria and
statistical analysis. The chi-square test and Mann-Whitney U test were
graft loss was observed in both cases. These patients did not receive
used for analysis. A P value
